if this holds up, method for following adjuvant treatment of breast cancer may change

[Lani]

After completing adjuvant treatment, most, naturally, hope for some way to tell if it was effective

There seems to be a lot of nihilism among oncologists that there really is nothing that can give that answer and probably never will be

I have previously suggested that serial bone marrow testing might give the answer, but oncologists seem to be averse to this suggestion (although when I ask them and discuss it with them at meetings, they finally admit that they never thought that patients might be more willing to undergo the procedure than they are willing to think about doing it, and realize they may be irrational about it)

In any case, they are desperately trying to get the same or similar information from circulating tumor cells and here is the latest:

ABSTRACT: Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer
[Annals of Oncology; Subscribe; Sample]

Background: Circulation of cancer cells in the blood is a mandatory step for metastasis, but circulating tumor cells (CTC) have a low metastatic efficiency in preclinical animal models. In this prospective study, we reported the clinical outcome of nonmetastatic breast cancer patients according to CTC detection.

Patients and methods: In 115 nonmetastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in a phase II trial (REMAGUS02).

Results: At baseline, 23% of patients were CTC positive, but only 10% had >1 CTC/7.5 ml of blood. After a median follow-up of 36 months, CTC detection before chemotherapy was an independent prognostic factor for both distant metastasis-free survival [DMFS; P = 0.01, relative risk (RR) = 5.0, 95% confidence interval (CI) 1.4-17] and overall survival (OS; P = 0.007, RR = 9, 95% CI 1.8-45). CTC detection after chemotherapy was of less significance (P = 0.07 and 0.09, respectively). Moreover, CTC detection showed interesting characteristics as an individual predictive test for metastatic relapses (sensibility 55%, specificity 81%, and global accuracy 77%).

Conclusions: Detection of ≥1 CTC/7.5 ml before neoadjuvant chemotherapy can accurately predict OS. Our findings may change the clinical management of nonmetastatic breast cancer and indicate that the metastatic efficiency of CTC could be higher than previously reported.

[bejuce]

Thank you for posting this, Lani. I participated in a trial at Stanford (Dr. Jeffrey's lab) to detect CTCs with a simple blood test. This was after my neo-adjuvant chemo, surgery, and radiation.

There were no CTCs found and I'm hopeful that that's a good thing. Good to see that the research is moving forward to use a simple blood test as a prognostic marker.

[Ellie F]

Hi Lani
I was interested to read your suggestion about serial bone marrow testing (especially as I have recently had one for low platelets!)
Could you elaborate what you think this would demonstrate in respect of mets etc.Hope this isn't a silly question!

Ellie

[Rich66]

They might want to retest CTC after neoadjuvant and surgery. There has been suggestion that Taxane neoadjuvant chemo as well as surgery increases CTCs.

[michka]

Rich, this finding about Taxol and CTC is important: "Interestingly, taxane treatment has been shown to increase the concentration of CTCs in the bloodstream more than 1000-fold when applied in advance of surgery"

I can't believe it. It's the standard treatment followed by most of us! This should be sorted out quickly.
Michka

[Rich66]

From what I understand, most of those CTCs aren't considered viable. But the more there are...

[Lani]

I just went to a lecture by Max Wicha. He is proceeding with a trial in collaboration with colleagues in Germany (where the oncologists aren't as adverse to performing bone marrows, it seems) where serial bone marrows will study the effects of different treatments, especially those which they hope will eradicated breast cancer stem cells.

He had lots of new data to present and said there would be 200 papers and posters on cancer stem cells at the upcoming AACR annual meeting!

He also thinks inflammation make have a role awakening the "sleeping beauty" dormant breast cancer stem cells and that her2 is not only a marker of the stem cells, with her2+ breast cancers having a higher percentage of stem cells within their tumors but that herceptin may be useful in some breast cancer patients who are not her2 FISH positive because it may target their cancer stem cells as well.

Have to run, but will try to answer Ellie's questions later...

[Lani]

Ellie--not a silly question at all.

Bone marrow micrometastases are felt to be cancer stem cells, which are known to be quite dormant ie, they only "wake up" and reproduce very rarely.

They are felt to be the cause of recurrences--even 20 years later.

I have previously written about them comparing them to mildew in a shower stall. You may use a Tilex (main ingredient bleach) and think you have killed it, but actually it hides out as a spore and only reappears when the conditions are right ie, dampness and starts growing again.

Chemotherapy has been shown not to get rid of these tumor cells in the bone marrow if they were there before treatment, as chemotherapy works on dividing cells and they are just hiding out and not dividing.

What wakes them up? Depending on whom you are talking to you may get different answers. Dr. Judah Folkmann felt an angiogenic switch was involved. Dr. Wicha thinks inflammation is involved among other things.

Sampling the bone marrow before and after treatment and periodically thereafter may be a way to determine if the treatment was effective, ie, getting rid not only of the bulky tumor, but also of the tumor cells hiding and sleeping in the bone marrow.

To me this seems much better than just waiting for mets to be visible to conventional testing, by which time most oncologists proclaim the patient uncurable. If the treatment given is found not to have gotten rid of these cells, additional treatments could be undertaken and perhaps prevent them from ever becoming MACROmetastases.

Hope this helped explain why I feel serial bone marrow testing may really help revolutionize breast cancer followup and treatment